Peripheral nerve stimulation for the treatment of chronic neuropathic pain

Abstract

Neuropathic pain is a chronic health condition with a severe impact on the quality of life of affected patients. The condition is often difficult to manage and refractory to traditional pain treatment strategies such as pharmacological management, physiotherapy and psychological therapy. Peripheral nerve stimulation has been proposed as an alternative treatment with numerous successful clinical reports. Nevertheless, the systematic understanding of the underlying mechanism of action is still limited. Efficacy studies in the form of randomised controlled trials have predominantly been conducted for occipital nerve stimulation to treat various headache conditions. Without trials of a wide range of neuropathic conditions, the commercial availability of approved medical devices is limited.

The overall objective of this thesis was to advance towards the development of a peripheral nerve stimulation system for a small-scale clinical trial that will be used to gain a deeper understanding of the underlying mechanisms of pain modulation. Design features of electrode arrays and new stimulation strategies were tested in order to facilitate the development of advanced clinical peripheral nerve stimulation systems.

The first part of the work consisted of the development of a small, wearable neural stimulator for the use in clinical trials. Chapter 2 presents the design and characterisation of the stimulator. It was shown that safe and efficacious neural activation could be achieved and the system will be suitable for use during a short-term clinical trial of electrode arrays with a percutaneous leadwire system.

In the second part, a model electrode setup was used to investigate a bipolar stimulation strategy. Chapter 3 documents an electrophysiological study on the maximisation of the therapeutic window available for stimulation. An electrode screening strategy was developed in order to increase the efficiency of intra- and post-operative testing of stimulation arrays with a large number of electrode combinations.

The third part of the work focussed on the development of single-source multipolar stimulation as a novel method to perform current focussing for increased selectivity of the neural activation. Chapter 4 presents the in vitro investigation that showed that a successful reduction of voltages at electrode sites other than the centre electrode was achieved when compared to monopolar stimulation. Furthermore, a significant improvement of the voltage reduction was also found compared to tripolar and common ground stimulation.

The promising results from the in vitro tests were followed by an in vivo evaluation as presented in Chapter 5. However, the focussing effects found in vitro did not translate to functional benefits in vivo for the investigated setup. Rather, increased neural activation thresholds were found resulting in potentially higher power requirements for a clinical system. Monopolar stimulation was identified as the favourable mode under the tested conditions.

In conclusion, the results of this thesis suggest that a safe and reliable, tailored electrode array in combination with a monopolar stimulation strategy forms a promising system in order to progress towards the overall objective, a short-term clinical trial. This will help to gain a deeper understanding of the underlying mechanism of action of peripheral nerve stimulation for the treatment of chronic neuropathic pain.